Poisonings by venomous animals are recognized as a problem of public health in some regions of the planet where the interaction of man with these animals is frequent. We can consider animals producing pharmacological substances which can interfere with our survival as venomous and/or venomous animals. The venoms most studied are those coming from snakes, scorpions, spiders, mollusks and microorganisms, however other venomous animals exist including fish, frogs, insects, anemones and corals, among others.
The antidotes based on manipulation of the immune system of mammals have been used to counteract the effects of the venom, where immunoglobulins or antibodies play the central role. In 1888 Emilie Roux and Alesandre Yersin demonstrated that the blood of animals immunized against diphtherial toxins provided protection to animals when defied against toxins. By 1890 Emil von Behring and Shibasaburo Kitasato confirmed the transfer of passive immunity against diphtheria and tetanus toxins; this year is considered the commencement of serum-therapy and is also thought of as the first generation of anti-venom, the second generation corresponds to purified immunoglobulins from serum and the following generation consists of immunoglobulin fragments.
The production of F(ab′)2 fragments and Fab, has been described in literature since the beginning of the last century, in 1936 I. A. Parfentjev (U.S. Pat. Nos. 2,065,196, 2,123,198 and 2,175,090). The majority of the methods are based on utilizing the physiochemical and thermodynamic properties of proteins, such as solubility, form and affinity. Therefore over the course of recent years some action has existed for the production of antibody fragments F(ab′)2 and Fab, as in the case of Landon U.S. Pat. No. 5,733,742, Sullivan et al., and U.S. Pat. No. 4,849,352.
However, the current development of protein analysis technologies has become a tool for the development and improvement of antibodies modified by enzymatic digestion, because they have allowed further characterization of the immunogens employed in the production of hyperimmune mammal plasmas, as well the quantification process of the neutralizing activity of specific antibodies, and control of the purification process.
The production of modified antibodies (fragments) takes placed when the immunoglobulins (IgG) are enzymatically digested guided by different proteolytic enzymes such as pepsin or papain, eliminating the fraction Fc in both cases but, in the case of pepsin, a fragment F(ab′)2 is obtained and in the case of papain, two fragments Fab. These fragments F(ab′)2 retain the characteristics of the complete antibodies with respect to their specificity, affinity and stability. In addition to the absence of region Fc from the antibodies, the appearance of adverse effects (such as, for example, anaphylactic reactions), is eliminated due to the fact that the Fc region bonding to various cell receptors such as the Fc receptor and other molecules of the immunity system such as the proteins of the complement, as well as other effector functions such as opzonization, cell lysis and the degranulation of the mast cell, basophils and eosinophils.
The Mexican patent MX230257 by J. Lopez de Silanes et al. of the Instituto Bioclon (Bioclon Institute), and its equivalents U.S. Pat. Nos. 6,709,655, 7,485,303 and 8,075,893, refer to the method for preparing a pharmaceutical composition comprising F(ab′)2s fragments, presenting unique characteristics acquired by the preparation method which is free of:
Complete antibody molecules
Proteic molecules of another nature
Albumin
Fibroinogen
Viral particles and
Pyrogens
However, not just any fabotherapeutic product comes within the scope of patent MX230257 and its United States equivalents.